ArticleNature communications2021
RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Structural and Energetic Determinants of Monobody Recognition of Oncogenic KRAS Variants.bioRxiv : the preprint server for biology · 2026Article
- De novo design of Ras isoform selective binders.Cell chemical biology · 2026Article
- AI accelerate the identification of druggable targets by 3D structures of proteins and compounds.NPJ precision oncology · 2026Review
- Emerging Therapeutic Landscapes for KRAS-Mutant Pancreatic Ductal Adenocarcinoma: Beyond the "Undruggable" Paradigm.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2026Review
- Adhirons are efficient tools to guide antiviral ligand discovery.Communications biology · 2025Article
- Structural characterization and inhibition of the interaction between ch-TOG and TACC3.The Journal of cell biology · 2025Article
- Article
- Use of Affimer technology for inhibition of α2-antiplasmin and enhancement of fibrinolysis.Blood advances · 2025Article
- Motif-guided identification of KRAS-interacting proteins.BMC biology · 2024Article
- Generating and validating renewable affimer protein binding reagents targeting SH2 domains.Scientific reports · 2024Article
- Targeting Grb2 SH3 Domains with Affimer Proteins Provides Novel Insights into Ras Signalling Modulation.Biomolecules · 2024Article
- IκBα kinase inhibitor BAY 11-7082 promotes anti-tumor effect in RAS-driven cancers.Journal of translational medicine · 2024Article
- Studying early structural changes in SOS1 mediated KRAS activation mechanism.Current research in structural biology · 2024Article
- Discovery of Hit Compounds Targeting the P4 Allosteric Site of K-RAS, Identified through Ensemble-Based Virtual Screening.Journal of chemical information and modeling · 2023Article
- Biological Applications of Synthetic Binders Isolated from a Conceptually New Adhiron Library.Biomolecules · 2023Article
- RAS degraders: The new frontier for RAS-driven cancers.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- The Nanotechnology-Based Approaches against Kirsten Rat Sarcoma-Mutated Cancers.Pharmaceutics · 2023Review
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- Eliminating oncogenic RAS: back to the future at the drawing board.Biochemical Society transactions · 2023Article
- Dynamic regulation of RAS and RAS signaling.The Biochemical journal · 2023Article
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 1 country.
Funding
Abstract
RAS mutations are the most common oncogenic drivers across human cancers, but there remains a paucity of clinically-validated pharmacological inhibitors of RAS, as druggable pockets have proven difficult to identify. Here, we identify two RAS-binding Affimer proteins, K3 and K6, that inhibit nucleotide exchange and downstream signaling pathways with distinct isoform and mutant profiles. Affimer K6 binds in the SI/SII pocket, whilst Affimer K3 is a non-covalent inhibitor of the SII region that reveals a conformer of wild-type RAS with a large, druggable SII/α3 pocket. Competitive NanoBRET between the RAS-binding Affimers and known RAS binding small-molecules demonstrates the potential to use Affimers as tools to identify pharmacophores. This work highlights the potential of using biologics with small interface surfaces to select unseen, druggable conformations in conjunction with pharmacophore identification for hard-to-drug proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.